Sunday, March 16, 2014

Human females appear to be
unique in the animal kingdom in that they live far beyond the end of
their fertility period. Typically,
menopause occurs in the 4th decade of life, and women can expect to
live to their 8th decade. In
men, however, fertility continues to near the end of life. In men, although there are clear declines affecting
the endocrine system, testicular function, and structure of the sperm chromosomes, there appears to be no andropause, that is, men retain a significant probability of fertility, but not women. (In
1935, three physicians reported what may be the oldest American father on record, a 94
year old North Carolina man who married a 27 year old widow and fathered a
child.)

In contrast to humans, in
chimpanzees fertility continues in both females and males until near the end of
life. That is, whereas in women menopause
is a mid-life event, in chimpanzee females it is a late-life event. Why?

A genetic wall of death beyond the fertility yearsIn 1966, W.D. (Bill) Hamilton, a just minted PHD student in biology, who would later be called "nature's oracle" because of his mathematical reasoning, and whose work would lay the foundation for the "selfish gene" of Richard Dawkins, used a mathematical model of genetics to demonstrate that from an evolutionary
standpoint, genes that protect against disease and expand the lifespan beyond
the age of fertility would tend to be eliminated with natural selection, and so animals should not live much longer than their end of
fertility. Bill's argument went as follows:
imagine four genes that are expressed in females and give immunity against some
lethal disease but are expressed only in one particular part of life. The first gene is expressed in the 1st
year of life, the second gene in the 15th year, the third gene in
the 30th year, and the fourth gene in the 45th. Now imagine that fertility ends before age of
45. If so, the fourth gene confers much
less advantage than the first three. This
model explained the fertility-age relationship in men, but could not explain
why women lose their fertility at around the midpoint of their life.

Evolutionary biologists have
been puzzled by the fact that human females have escaped this “wall of death” that,
at least theoretically, looms after menopause, and appears to be present in
many other animals. Numerous theories
have been offered. Perhaps in the past, human longevity was too short for females to experience menopause (defined as
surviving for at least one year in good health beyond the last menstrual cycle),
and so menopause is a byproduct of increased longevity unique to humans. Perhaps by entering into menopause, older
mothers increased the survival probability of their children and grandchildren
(grandmother effect). Perhaps
reproductive aging was more severe than somatic aging, and so unlike other
functions that could proceed at less than some high level of accuracy,
reproduction in females could not, and therefore stopped when a threshold level of
accuracy was reached.

The jury is still out on
whether any of these theories are supported by evolutionary data. However, the most interesting new hypothesis
proposes that women experience menopause at mid-life because of behavior of
men.

Male sexual preference may lead to female menopause

In 2007, Shripad
Tuljapukar and colleagues revisited Hamilton’s mathematical model of human
evolution and like Hamilton assumed that there were genes that gave resistance
to fatal diseases at certain age of life.
Unlike Hamilton, they assumed these genes existed in both males and females. They added to Hamilton’s model a matrix representing
mating preference. In this matrix, \$ M_{i,j}
\$ represented the probability of a male age \$ i \$ to mate with a female of
age \$ j \$, and if both were fertile, to produce an offspring. They found that if there was a gene that gave
resistance to a fatal disease at say the 45th year in women, and
this gene did the same thing in men, then both men and women would benefit from
this gene because the older men would continue to be fertile and produce babies with
the younger women. The interesting idea was that selection would favor survival
of both males and females as long as one of the two groups could reproduce with the
fertile sub-population of the other group.

But this idea was not
entirely satisfactory because the same model would predict that it was better if
females could extend their fertility period and like males, never experience
menopause. Sure, having one group live
longer than the menopause age of another group would make both groups live
longer, but why did natural selection produce menopause in females, but not males? That is, what is the origin of female menopause in the first place?

In 2013, Richard Morton
and colleagues used a similar mathematical model of genetic evolution,
but started with the assumption that prolonged fertility was the ancestral
state of both males and females. That
is, they assumed that at some distant past, neither males nor females experienced menopause. They also assumed
existence of a sex-specific infertility causing mutation in the genome which would produce menopause. They asked about the conditions that might lead to this gene being expressed early in females, but not males.

They found that if males and females had no
preference for the age of their partner, then infertility-causing mutations
would not become sex specific. That is, if
the age of the partner did not matter to a male or a female, reflected in the matrix \$ M_{i,j} \$, then both males
and females would remain fertile into old age.
However, if males preferred younger females, then something interesting
happened: female fertility declined without a loss in their longevity,
resulting in female menopause, but male menopause never occurred. The interesting idea was that a male
preference for mating with a younger female would specifically affect fertility
in females, limiting it and producing menopause.

An amazing prediction of
this model is that evolution could have proceeded in a very different path: if females had shown a
preference for mating with younger males, then fertility would have declined in the older males,
resulting in male menopause, while allowing females to maintain fertility into old age.

Ramajit Raghav, an Indian man who was reported to have fathered a child at 97 years of age.

References

R. Caspari and S.H. Lee (2004) Older age becomes
common late in human evolution. Proceedings of the National Academy of Science 101:10895-10900.

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About Me

I was born in Iran and immigrated to the US at the age of 14. I was educated at Gonzaga University, University of Southern California, and finally MIT. I studied under the mentorship of Prof. Michael Arbib and Prof. Emilio Bizzi. I am currently Professor of Biomedical Engineering and Neuroscience, and the Director of the BME PhD Program at Johns Hopkins School of Medicine. I am a neuroscientist who uses mathematics to understand how the brain controls our movements.